The central focus of Project 0019 is to correlate clinical observations with laboratory results to generate hypotheses regarding tumor progression or response to therapy, and to test these new hypotheses in the clinic. Clinical observations will result from studies focused on select hematologic malignancies and breast cancer. Patterns of tumor progression and treatment failure will serve to guide the laboratory cores and projects to produce new approaches to overcoming drug resistance using novel drugs, chemosensitizers, or changes in drug schedule or dosing. The specific aims of project are: 1. To present clinical observations as hypotheses for laboratory investigations and refinements of laboratory directions; 2. To develop new therapeutic approaches for select hematologic malignancies and breast cancer using leads developed in the laboratory; 3. To study the biology and scientifically based new therapy of cancers by interrelating clinical observations and treatment outcome with pharmacokinetics, in vivo and in vitro models for drug development, and the investigation of drug resistance; 4. To test hypotheses generated by investigators of laboratory projects.